Tissue Factor Detection for Selectively Discriminating Unstable Plaques in an Atherosclerotic Rabbit Model

Journal of Nuclear Medicine

Kantaro Nishigori¹  Seigo Ishino¹  Yuji Kuge¹  Yuki Ogawa¹  Nozomi Takai¹  Hideo Saji¹  Takashi Temma¹  Masashi Shiomi¹  Masahiro Ono¹ 

关键词: tissue factor;    radioimmunodetection;    thrombus;    atherosclerotic plaque;   

DOI  :  10.2967/jnumed.110.081216

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Tissue factor (TF), a transmembrane glycoprotein that acts as an essential cofactor to factor VII/VIIa, initiates the exogenous blood coagulation cascade leading to thrombin generation and subsequent thrombus formation in vivo. TF expression is closely related to plaque vulnerability, and high TF expression is shown in macrophage-rich atheromatous lesions, making TF a potential target for detecting atheromatous lesions in vivo. Thus, we prepared 99mTc-labeled anti-TF-monoclonal antibody (TF-mAb) IgG as a molecular probe and evaluated its usefulness to achieve TF-specific imaging using myocardial infarction–prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Methods: Anti-TF-mAb was created using a standard hybridoma technique and was labeled by 99mTc with 6-hydrazinonicotinic acid (HYNIC) as a chelating agent to obtain 99mTc-TF-mAb. The immunoreactivity of HYNIC-TF-mAb was estimated by flow cytometry. WHHLMI and control rabbits were injected intravenously with 99mTc-TF-mAb. Twenty-four hours after the injection, the aorta was removed and radioactivity was measured. Autoradiography and histologic studies were performed using serial aorta sections. Subclass matched antibody (IgG1) was used as a negative control. Results: HYNIC-TF-mAb showed 93% immunoreactivity of the anti-TF-mAb. The radioactivity accumulation in WHHLMI aortas was 6.1-fold higher than that of control rabbits. Autoradiograms showed a heterogeneous distribution of radioactivity in the intima of WHHLMI aortas. Regional radioactivity accumulation was positively correlated with TF expression density (R = 0.64, P < 0.0001). The highest radioactivity accumulation in percentage injected dose × body weight/mm2 × 102 was found in atheromatous lesions (5.2 ± 1.9) followed by fibroatheromatous (2.1 ± 0.7), collagen-rich (1.8 ± 0.7), and neointimal lesions (1.8 ± 0.6). In contrast, 99mTc-IgG1 showed low radioactivity accumulation in WHHLMI aortas that was independent of the histologic grade of lesions. Conclusion: The TF-detecting ability and preferential accumulation in atheromatous lesions of 99mTc-TF-mAb were demonstrated, indicating its potential for selective imaging of macrophage-rich atheromatous lesions in vivo.

【 授权许可】

Unknown